Antidotes to antisense compounds

Abstract

The present invention relates to antisense antidote compounds and uses thereof. Such antidote compounds reduce the magnitude and/or duration of the antisense activity of an antisense compound.

1. A method of reducing the activity of an antisense compound comprising identifying an animal that has received an antisense compound and administering to said animal an antidote compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to said antisense compound. 
     
     
       2. The method of  claim 1 , wherein the animal is a human. 
     
     
       3. A method of inhibiting antisense activity in a cell comprising contacting the cell with an antidote compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to an antisense compound and thereby inhibiting the antisense activity in the cell. 
     
     
       4. The method of  claim 3 , wherein the cell is in an animal. 
     
     
       5. The method of  claim 4 , wherein the animal is a human. 
     
     
       6. A method comprising:
 contacting a cell with an antisense compound; 
 detecting antisense activity; and 
 contacting the cell with an antidote compound. 
 
     
     
       7. The method of  claim 6 , wherein the antidote compound comprises a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to said antisense compound. 
     
     
       8. The method of  claim 6 , wherein the detecting antisense activity comprises measuring a parameter selected from the group consisting of an amount of target mRNA present, an amount of target protein present, and an activity of a target protein. 
     
     
       9. A method of ameliorating a side-effect of antisense treatment comprising:
 contacting a cell with an antisense compound; 
 detecting a side-effect; 
 contacting the cell with an antidote compound; and 
 thereby ameliorating the side effect of the antisense compound. 
 
     
     
       10. The method of  claim 9 , wherein the antidote compound comprises a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to said antisense compound. 
     
     
       11. A method of treating a patient comprising:
 administering to the patient an antisense compound; 
 monitoring the patient for antisense activity; and 
 if the antisense activity becomes higher than desired, administrating an antidote compound. 
 
     
     
       12. The method of  claim 11 , wherein the antidote compound comprises a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to said antisense compound. 
     
     
       13. The method of  claim 11 , wherein the monitoring antisense activity comprises measuring a parameter selected from the group consisting of an amount of target mRNA present, an amount of target protein present, and an activity of a target protein. 
     
     
       14. The method of  claim 11  further comprising detecting antidote activity by measuring antisense activity after administration of the antidote compound. 
     
     
       15. The method of  claim 11 , wherein the patient is a human. 
     
     
       16. A method of treating a patient comprising:
 administering to the patient an antisense compound; 
 monitoring the patient for one or more side effect; and 
 if the one or more side effect reaches an undesirable level, administrating an antidote compound. 
 
     
     
       17. The method of  claim 16 , wherein the antidote compound comprises a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to said antisense. 
     
     
       18. The method of  claim 16 , wherein the patient is a human.